Respiratory system diseases caused by respiratory viruses are common and exert tremendous pressure on global healthcare system. In our previous studies, we found that Long non-coding RNA NRAV (Lnc NRAV) and its target molecule Rab5c plays a significant role in respiratory virus infection. However, the mechanism by which Rab5c affects virus replication remains unclear. Rab5c, a protein mainly localized on the cell membranes and in early endosomes and phagosomes, participates in endocytosis mediated by clathrin and regulates the fusion of early endosome, maturation of early phagosomes, and autophagy. Therefore, we inferred that Rab5c impacts virus replication, which might be related to endocytosis or autophagy. We selected RSV (respiratory syncytial virus) as a representative enveloped virus and ADV (Adenovirus) as a representative non-enveloped virus to explore the possible mechanism of RSV and ADV replication promoted by Rab5c in A549 cells and in Rab5c-overexpressing mice. Here, we confirmed that the activated Rab5c promotes RSV and ADV replication and the inactivated Rab5c inhibits their replication. However, Rab5c promoting RSV and ADV replication is not mediated by endocytosis rather by autophagy in respiratory epithelial cells. Our study showed that Rab5c upregulates LC3-Ⅱ (microtubule-associated protein 1 light chain 3 beta) protein expression levels by interacting with Beclin1, a key autophagy molecule, which can induce autophagy and promote replication of ADV and RSV. This study enriches the understanding of the interaction between respiratory viruses and Rab5c, providing new insights for virus prevention and treatment.

由呼吸道病毒引起的呼吸系统疾病很常见，给全球医疗保健系统带来巨大压力。在我们前期的研究中，我们发现长链非编码RNA NRAV（Lnc NRAV）及其靶分子Rab5c在呼吸道病毒感染中发挥着重要作用。然而，Rab5c影响病毒复制的机制仍不清楚。Rab5c是一种主要定位于细胞膜、早期内体和吞噬体中的蛋白质，参与网格蛋白介导的内吞作用，调节早期内体的融合、早期吞噬体的成熟和自噬。因此，我们推测Rab5c影响病毒复制，这可能与内吞作用或自噬有关。我们选择RSV（呼吸道合胞病毒）作为代表性的包膜病毒和ADV（腺病毒）作为代表性的非包膜病毒，以探讨Rab5c在A549细胞和Rab5c过表达小鼠中促进RSV和ADV复制的可能机制。在这里，我们证实激活的 Rab5c 促进 RSV 和 ADV 复制，而失活的 Rab5c 抑制它们的复制。然而，Rab5c 促进 RSV 和 ADV 复制的作用不是通过内吞作用介导的，而是通过呼吸道上皮细胞中的自噬介导的。我们的研究表明，Rab5c通过与关键自噬分子Beclin1相互作用上调LC3-Ⅱ（微管相关蛋白1轻链3β）蛋白表达水平，从而诱导自噬并促进ADV和RSV的复制。这项研究丰富了对呼吸道病毒与Rab5c相互作用的理解，为病毒预防和治疗提供了新的见解。